Clouston syndrome

Genetic testing can be offered to other family members if a GJB6 gene mutation is found in an affected person. For example, if a child is found to have a GJB6 gene mutation, testing should first be offered to the child’s parents. If the mother or father is found to have the same GJB6 gene mutation, testing can then be offered to the parent’s other children, siblings, and parents.

Support groups for Clouston syndrome and groups for certain features of the condition can be great places to find other people with the condition. Some of these groups include:

National Foundation for Ectodermal Dysplasias
6 Executive Drive, Suite 2
Fairview Hights, IL 62208, USA
Phone: (618) 566-2020
Email: [email protected]
Website: http://www.nfed.org

Ectodermal Dysplasia Society
Unit 1 Maida Vale Business Centre
Leckhampton, England
GL53 7ER, United Kingdom
Phone: 4401242261332
Toll-free: 4407805775703
Email: [email protected]
Website: http://www.ectodermaldysplasia.org

Ectodermal Dysplasias International Registry
National Foundation for Ectodermal Dysplasias
410 East Main Street
Mascoutah IL 62258
Phone: 618-566-2020
Fax: 618-566-4718
Email: [email protected]

There are several sites that have patient stories about people living with genetic diseases:

ThinkGenetic – This site has a growing database of patient stories from patients around the world. You can read patient stories about Clouston syndrome here. If there is not a story, please consider adding your story.
Rare Diseases Europe offers stories from people with all types of rare genetic conditions. You can browse through the stories with pictures of the individuals who wrote them.

Although the teeth are often affected in other types of ectodermal dysplasia, the teeth are typically normal in individuals with Clouston syndrome.

In other forms of ectodermal dysplasia, people may have abnormalities with their sweat glands causing them to have problems sweating. However, people with Clouston syndrome do not typically have problems with their sweat glands or their ability to sweat.

In order to receive the best medical care, people with Clouston syndrome should see the following medical specialists:

There can be skin differences in people with Clouston syndrome. The skin on the palms of the hands and the soles of the feet can be thickened (palmoplantar hyperkeratosis) and typically gets worse as one gets older. The skin over the joints may be darker in color (hyperpigmentation). The fingertips may also be wider and rounder than expected (clubbing).

People with Clouston syndrome may have differences in their nails. During the first year of life, the nails may appear white. Over the course of one’s lifetime, the nails will grow slowly and may become malformed, thickened, or small. This is called nail dystroph and is considered the most noticeable feature of Clouston syndrome.

The usual abbreviation for Clouston syndrome is HED2. This stands for hidrotic ectodermal dysplasia 2.

The prognosis for individuals with Clouston syndrome is positive. The life span is predicted to be normal and there are no developmental concerns.

Clouston syndrome is a genetic condition that can affects a person’s hair, nails, and skin. This condition is just one in a group of over 150 conditions known as ectodermal dysplasias. In these individuals, hair can be sparse, lighter in color, patchy, fragile, and/or absent. Fingernails and toenails can be malformed, small, and/or thickened. Skin on the hands and feet can be thick, and the skin over joints may also be darker in color. Teeth and sweat glands are typically not affected in Clouston syndrome. Not everyone with Clouston syndrome experiences the same signs or symptoms.

People with Clouston syndrome may have hair that is sparse, fine, brittle, light in color, patchy, or absent. Patchy or absent hair can also be called partial or total alopecia. The eyebrows, eyelashes, pubic, and armpit (axillary) hair may also be sparse or absent. Hair problems may get worse as a person with Clouston syndrome goes through puberty.

Everyone has two copies of the GJB6 gene located on chromosome 13. The official name of this gene is “gap junction protein beta 6.” We get one copy of the GJB6 gene from our mother and one copy from our father. Having a specific harmful change (mutation) in one copy of the GJB6 gene causes Clouston syndrome.

When a person inherits a “variant” or "variant of unknown significance" in the gene that causes Clouston syndrome, it means they have a change in the GJB6 gene. However, at the current time, there is not enough research or evidence to show whether that specific change actually causes the symptoms of Clouston syndrome. As more individuals are tested and found to have that specific change and more research is performed, sometimes the interpretation of a variant will change.

Genotype-phenotype correlation means that a specific change in a gene causes specific medical concerns. There is genotype-phenotype correlation for GJB6 gene mutations and Clouston syndrome:

Clouston syndrome is a genetic condition that can affect a person’s hair, nails, and skin. It is a form of ectodermal dysplasia. Hair can be sparse, lighter in color, patchy, fragile, and/or absent. Fingernails and toenails can also be malformed, small, and/or thickened. Skin on the hands and feet can be thick, and skin over joints may be darker in color. Teeth and sweat glands are typically not affected. Not everyone with Clouston syndrome experience the same signs or symptoms.

After the diagnosis of Clouston syndrome, it is important to identify the person’s specific needs. The nails, hair, and skin should be looked at closely. A referral to a dermatologist may be made and a genetics appointment can help with genetic testing for the affected individual and other family members.

There are treatments for features of Clouston syndrome. They include:

Each state has a newborn screen which includes a group of genetic conditions. Clouston syndrome is not included in any newborn screens in the United States. If there is a family history of Clouston syndrome or if Clouston syndrome is suspected at birth, genetic testing can be ordered. This testing is usually performed on a blood sample either collected from the umbilical cord or from a normal blood draw.

As of 2019, only the GJB6 gene is known to be associated with Clouston syndrome. Genetic testing involves looking at this gene for specific changes. There are four GJB6 gene mutations to most commonly cause Clouston syndrome.
Imagine that the GJB6 gene is a long sentence. This sentence tells the body how to grow and develop. One type of genetic testing is called sequencing. Sequencing looks for spelling errors in this sentence. It can find a letter that is in the wrong place. Another type of genetic testing is called deletion/duplication testing. Deletion/duplication testing looks for larger pieces of missing (deleted) or extra (duplicated) information, like words in the sentence.
If the sentence has spelling errors or missing/extra words, it might not make sense. The body then grows and develops differently. The result is a genetic condition.
The first genetic test that should be done will look for the four specific GJB6 mutations known to be associated with Clouston syndrome. If this testing is unrevealing, sequencing of the whole GJB6 gene should be done. Deletion/duplication testing is usually not offered for Clouston syndrome because no mutations are known to be picked up through this analysis.
If there is a known GJB6 gene mutation in the family, testing can specifically look for this mutation in other family members. This is called site-specific analysis.
Some labs offer ectodermal dysplasia panels that look at many different genes at once. These panels might include the GJB6 gene.
A medical geneticist or genetic counselor can help you understand more about the testing process. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

There is no cure for Clouston syndrome. Treatment is limited to management and surveillance of the features of the condition.

No. People with Clouston syndrome can be affected differently. It is difficult to predict which specific medical concerns an individual will experience. Some people will be more mildly affected and some people will be more severely affected. Even multiple people in the same family who have Clouston syndrome can be affected differently.

Clouston syndrome is relatively common in the French-Canadian population of southwest Quebec. The condition has also been reported in African, Chinese, French, Indian, Malaysian, Scottish, Spanish, and Ashkenazi Jewish populations.

If someone has Clouston syndrome, their primary care provider should do a thorough exam of their nails, hair, and skin. The primary care provider might refer the person to a dermatologist (skin doctor) and medical geneticist.

If a person is affected with Clouston syndrome and has a known GJB6 gene mutation, there is a 50% chance that each of his/her children will be affected. However, the clinical features and severity of these features cannot be predicted.

If a parent has Clouston syndrome and a known GJB6 gene mutation, genetic testing can be done during a pregnancy. Chorionic villus sampling (CVS) and amniocentesis are procedures that can be done during a pregnancy. These procedures are invasive and can pose a small risk for miscarriage or loss of the pregnancy.
CVS involves removing a small piece of the placenta and sending it to a laboratory for genetic testing. CVS can be performed around 10-12 weeks of gestation.
Amniocentesis involves taking a sample of amniotic fluid and sending that sample to a laboratory for genetic testing. This testing can be performed starting at 15 weeks of gestation.
Testing will look for the same GJB6 gene mutation found in the parent. Testing cannot predict the baby’s clinical features.
If you are interested in prenatal testing for Clouston syndrome, you can speak with a genetic counselor in your area. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

When a child has a change or mutation in the GJB6 gene, it is most often passed down or inherited from a parent. A small percentage of the time there is no family history and the change in the GJB6 gene is a new change in the child’s DNA.

As of 2019, at least four GJB6 gene mutations known to be associated with Clouston syndrome. They are often written as followed:

Clouston syndrome is inherited in a autosomal dominant pattern. Everyone has two copies of their GJB6 gene. One copy of the gene comes from your mother and the other copy comes from your father. When a person has a specific change (mutation) in one copy of their GJB6 gene, they have a genetic diagnosis of Clouston syndrome.

Genetic testing for Clouston syndrome can be ordered by a geneticist or genetic counselor. At your appointment, you will talk about your medical history and about your family members and their medical concerns. The doctor will do a physical examination. You will get information about testing and if you decide you want genetic testing, you can give consent (permission). This might happen in one visit, or over a few visits.
Each clinic works differently and sometimes the clinic checks with your insurance about coverage for testing, but it could also be your responsibility. If you choose to do genetic testing, a blood sample and signed paperwork is sent to a laboratory. Your results are sent back to the geneticist and genetic counselor and they will contact you with results.

The GJB6 gene provides instructions for making the protein connexin 30. Connexin 30 proteins form channels that transport small molecules. This protein is found in many different tissues in the body such as the skin, hair follicles, and nail beds. When this protein does not work, you see the skin, hair, and nail abnormalities common in Clouston syndrome.

Clinical research can be found at the following:

Unfortunately, as of 2019, there is no center of excellence for Clouston syndrome. One resource for people who want to find out more about treatment for Clouston syndrome is The National Foundation for Ectodermal Dysplasias.

It is currently unknown how many people are affected by Clouston syndrome. It is more common in the French-Canadian population, but it has been reported in many other populations as well.

Genetic testing for Clouston syndrome typically involves a blood sample but some laboratories accept saliva samples. Skin or muscle samples taken via biopsy are not usually used for genetic testing to diagnose Clouston syndrome.

Approximately 100% of people with Clouston syndrome have a gene change (mutation) in the GJB6 gene. As of 2019, there is no other gene associated with Clouston syndrome.

Almost everyone with a specific GJB6 gene mutation for Clouston syndrome has hair, skin, and/or nail findings. The specific features and the severity of the features can be different for different people.

People with Clouston syndrome do not typically have developmental delay or require extra help in school.

Yes. There is a technology called preimplantation genetic diagnosis (PGD) that may be available if the family has a known GJB6 gene mutation.
Embryos are made in a laboratory using the mother’s egg cells and the father’s sperm cells. Genetic testing can then be done to see if the GJB6 gene mutation is present. Embryos that don’t have the GJB6 gene mutation can then be implanted in the mother.
If you are interested in preimplantation genetic diagnosis, you can speak with a genetic counselor who specializes in assisted reproductive technology. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Clouston syndrome is just one of over 150 types of ectodermal dysplasias. In these conditions, the skin, hair, nails, teeth, and/or sweat glands can be affected. Not all of these are affected in every type of ectodermal dysplasia.

There are other names for Clouston syndrome. They include the following:

There are support groups for Clouston syndrome. Some of these groups are specific for Clouston syndrome, and others are groups for certain features of this condition. Support groups include the following:

National Foundation for Ectodermal Dysplasias
6 Executive Drive, Suite 2
Fairview Hights, IL 62208, USA
Phone: (618) 566-2020
Email: [email protected]
Website: http://www.nfed.org

Ectodermal Dysplasia Society
Unit 1 Maida Vale Business Centre
Leckhampton, England
GL53 7ER, United Kingdom
Phone: 4401242261332
Toll-free: 4407805775703
Email: [email protected]
Website: http://www.ectodermaldysplasia.org

Ectodermal Dysplasias International Registry
National Foundation for Ectodermal Dysplasias
410 East Main Street
Mascoutah IL 62258
Phone: 618-566-2020
Fax: 618-566-4718
Email: [email protected]

Genetic and Rare Diseases (GARD) Information Center
PO Box 8126
Gaithersburg, MD 20898-8126
Phone: (301) 251-4925
Toll-free: (888) 205-2311
Website: http://rarediseases.info.nih.gov/GARD/

March of Dimes
1275 Mamaroneck Avenue
White Plains, NY 10605
Phone: (914) 997-4488
Email: [email protected] or [email protected]
Website: http://www.marchofdimes.org and nacersano.org

Locks of Love
234 Southern Blvd.
West Palm Beach, FL 33405-3099
Phone: (561) 833-7332
Toll-free: (888) 896-1588
Email: [email protected]
Website: http://www.locksoflove.org

GJB6 gene mutations are associated with other conditions. They are the following:

There are other genetic conditions that are similar to Clouston syndrome. Some similar conditions include: